Portopulmonary Hypertension: Treatment

Tadalafil

Tadalafil is another oral PDE-5 inhibitor but with a longer half-life than sildenafil. Unlike sildenafil, which requires 3 times daily dosing, tadalafil requires once daily administration. A few case reports have demonstrated tadalafil’s effectiveness for POPH in combination with other medical therapy (eg, sildenafil, ambrisentan).^30,31

Guanylate Cyclase Stimulator

Riociguat

Riociguat is a first-in-class activator of soluble form of guanylate cyclase that increases levels of cyclic GMP. Two randomized clinical trials, PATENT, a study in PAH patients, and CHEST, a study in patients with chronic thromboembolic pulmonary hypertension showed improvement in 6MWD at 12 weeks (PATENT) or 16 weeks (CHEST), with improvement in secondary endpoints such as PVR, N-terminal pro b-type natriuretic peptide and WHO functional class.^32,33 Riociguat may have potential advantages in patients with POPH given that it has a favorable liver safety profile. A subgroup analysis of patients enrolled in the PATENT study showed that 13 had POPH and 11 were randomized to receive riociguat 2.5 mg 3 times daily dose and 2 received placebo.³⁴ Riociguat was well tolerated and improved 6MWD that was maintained over 2 years in the open label extension.

Medications to Avoid

Nonselective beta-blockers are commonly recommended in patients with portal hypertension to help prevent variceal hemorrhage. However, in patients with POPH, beta-blockers have been shown to decrease exercise capacity and worsen pulmonary hemodynamics. A study of 10 patients with moderate to severe POPH who were receiving beta-blockers for variceal bleeding prophylaxis showed that 6MWD improved in almost all of the patients, cardiac output increased by 28%, and PVR decreased by 19% when beta-blockers were discontinued.³⁵ The authors concluded that the use of beta-blockers should be avoided in this patient population.

Calcium channel blockers should not be used in patients with POPH because they can cause significant hypotension due to systemic vasodilatation and decreased right ventricular filling. Patients with portal hypertension and chronic liver disease commonly have low systemic vascular resistance and are particularly susceptible to the deleterious effects of calcium channel blockers.

Transplantation

Liver transplantation is a potential cure for POPH and its role in POPH has evolved over the past 2 decades. In 1997, Ramsay et al published their review of 1205 consecutive liver transplants at Baylor University Medical Center (BUMC) in Texas.³⁶ The incidence of POPH in this group was 8.5%, with the majority of patients having mild POPH. Liver transplant outcomes were not affected by mild and moderate pulmonary hypertension. However, patients with severe POPH (n = 7, systolic pulmonary artery pressure > 60 mm Hg) had a mortality rate of 42% at 9 months post-transplantation and 71% at 36 months post-transplant. The surviving patients continued to deteriorate with progressive right heart failure and no improvement in POPH.